Gonick H C, Weiler E W, Khalil-Manesh F, Weber M A
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Am J Hypertens. 1993 Aug;6(8):680-7. doi: 10.1093/ajh/6.8.680.
Circulating inhibitors of the transport enzyme, sodium-potassium-activated adenosine triphosphatase (Na(+)-K(+)-ATPase), have been shown to be of possible pathogenetic importance in the mechanism of essential hypertension. Although previous studies have demonstrated the presence of both high molecular weight (HMW) and low molecular weight (LMW) natriuretic plasma Na(+)-K(+)-ATPase inhibitors, no previous attempts have been made to ascertain whether HMW or LMW forms predominate in hypertension. In this study, plasma samples obtained from 26 patients with essential hypertension, 12 normotensive controls, and six normotensives with a family history of hypertension, were separated into HMW and LMW moieties by passage through a 1 kDa Amicon membrane. The LMW moiety was separated on C18 Sep-Pak cartridges, applying a 10% step-wise acetonitrile trifluoroacetic acid gradient. The HMW moiety was further separated on Sephadex G-75. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the fraction with inhibitory activity contained a distinct 12 kDa protein band, with staining intensity depending on the presence or absence of hypertension. Na(+)-K(+)-ATPase inhibitory activity was found in several LMW fractions, but differences between hypertensives and normotensives were observed in only one fraction (0.29 +/- 0.12 SD v 0.11 +/- .12 mumol/L ouabain equivalents, P < .01). Na(+)-K(+)-ATPase inhibitory activity in the HMW fraction was 38 x the inhibitory activity in the LMW fraction and was significantly increased in hypertensives as compared to normotensive controls (10.9 +/- 8.9 v 1.3 +/- 0.8 mumol/L ouabain equivalents, P < .01). Inhibitory activity in both HMW and LMW fractions correlated positively with mean blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
转运酶钠钾激活三磷酸腺苷酶（Na(+)-K(+)-ATPase）的循环抑制剂已被证明在原发性高血压机制中可能具有致病重要性。尽管先前的研究已证明存在高分子量（HMW）和低分子量（LMW）的利钠血浆Na(+)-K(+)-ATPase抑制剂，但此前尚未有人试图确定在高血压中HMW或LMW形式是否占主导。在本研究中，从26例原发性高血压患者、12例血压正常对照者以及6例有高血压家族史的血压正常者获取的血浆样本，通过1 kDa的Amicon膜过滤分离为HMW和LMW部分。LMW部分在C18 Sep-Pak柱上分离，采用10%逐步乙腈三氟乙酸梯度。HMW部分在Sephadex G-75上进一步分离。十二烷基硫酸钠聚丙烯酰胺凝胶电泳显示，具有抑制活性的部分含有一条明显的12 kDa蛋白带，染色强度取决于是否存在高血压。在几个LMW部分中发现了Na(+)-K(+)-ATPase抑制活性，但仅在一个部分中观察到高血压患者和血压正常者之间的差异（0.29±0.12 SD对0.11±0.12 μmol/L哇巴因当量，P<0.01）。HMW部分中的Na(+)-K(+)-ATPase抑制活性是LMW部分中抑制活性的38倍，与血压正常对照者相比，高血压患者中显著增加（10.9±8.9对1.3±0.8 μmol/L哇巴因当量，P<0.01）。HMW和LMW部分的抑制活性均与平均血压呈正相关。（摘要截取自250字）
